Facile synthesis of 3-arylpyrroles by tandem Suzuki-dehydrogenation reaction

Article abstract of DOI:10.1016/S0040-4039(00)00392-0

Facile method for the synthesis of 3-arylpyrroles is described based on the palladium-catalyzed coupling of trifluoromethanesulfonic acid 1-benzyl- 2,5-dihydro-1H-pyrrol-3-yl ester with aryl halides. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00392-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3423–3425
Facile synthesis of 3-arylpyrroles by tandem
Suzuki–dehydrogenation reaction
Chi-Wan Lee ∗ and Yong Jun Chung
Department of Chemistry, Center for Superfunctional Materials, Pohang University of Science and Technology, San 31,
Pohang 790-784, South Korea
Received 18 January 2000; revised 1 March 2000; accepted 3 March 2000
Abstract
Facile method for the synthesis of 3-arylpyrroles is described based on the palladium-catalyzed coupling
of trifluoromethanesulfonic acid 1-benzyl-2,5-dihydro-1H-pyrrol-3-yl ester with aryl halides. © 2000 Elsevier
Science Ltd. All rights reserved.
Keywords: pyrroles; Suzuki reaction; dehydrogenation; palladium and compounds.
The introduction of substituents into the 3-position of pyrrole has been actively pursued in recent
years due to the importance of this class of compound in natural product synthesis.1 In contrast to the
significant number of preparations of polysubstituted 3-arylpyrroles,2 there are relatively few syntheses
of simple 3-arylpyrroles. A literature survey on the preparation of 3-arylpyrrole showed that some of
the methods reported involve the reductive cyclization of 2-arylsuccinonitriles,3 the base-induced ring
closure of arylvinamidinium salts,4 and rhodium-catalyzed hydroformylation of β-alkynylamines with
CO/H2.5
We now report that reaction of trifluoromethanesulfonic acid 1-benzyl-2,5-dihydro-1H-pyrrol-3-yl
ester (2) with aryl halides in the presence of palladium-catalyzed leads to the formation of 3-arylpyrroles
(3) in good yields (see Scheme 1 and Table 1).
Scheme 1.
The synthesis was carried out using commercially available 1-benzyl-3-pyrrolidinone (1) as the
starting material. Vinyl triflate (2)6 could be prepared in 55% yield from 1-benzyl-3-pyrrolidinone
∗
Corresponding author. Fax: 82-562-279-8137; e-mail: chiwan@chem.postech.ac.kr (C.-W. Lee)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00392-0
tetl 16672

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Table 1
Tandem Suzuki–dehydrogenation reaction
(1) by trapping the enolate with a triflating reagent, N-phenyltrifluoromethanesulfonimide (Tf2NPh).7
The regiochemistry of enolization of α-amino ketone has been investigated by A. R. Martin et al.8 In
accordance with his result, when the N-substituents are electron-donating groups (methyl, benzyl), only
allylamine-type isomers were detected, and if the substituents are electron-withdrawing groups (Cbz,
Boc), the enamine-type isomers were exclusively observed. As expected, the reaction took place in
such a manner that it gives exclusively allylamine-type triflate (2) rather than enamine-type isomer,
determined by NOE experiments. We have treated the vinyl triflate (2) with boronic acid derivatives
in the presence of a catalytic amount of Pd(PPh3)4 and KOAc in dioxane at 100°C.9 The reaction
mixture provided a compound, which was isolated and characterized to be 3-arylpyrroles. Apparently,
after Suzuki coupling, subsequent dehydrogenation was occurred providing 3-arylpyrroles. In general,
dehydrogenative aromatizations can be achieved by heating (300∼350°C) hydroaromatic compounds
with catalytic amounts of palladium on activated carbon.10 In our reaction, under the Suzuki coupling
condition, the dehydrogenative aromatization11 of the pyrroline (2) took place in tandem mode. This
could be the first example of tandem Suzuki–dehydrogenation reaction to prepare 3-arylpyrroles from
pyrroline.
References
1. Anderson, H. J.; Loader, C. E. Synthesis 1985, 353–364 and references cited therein.
2. Bean, G. T. In Pyrroles. Part 1: The Synthesis of 1H-Pyrroles; Jones, R. A., Ed.; John Wiley and Sons: New York, 1990;
pp. 105–294. Gupta, R. R.; Kumar, M.; Gupta, V. Heterocyclic Chemistry; Springer: Heidelberg, 1999; Vol. 2, pp. 34–43.
3. Babler, J. H.; Spina, K. P. Tetrahedron Lett. 1984, 25, 1659–1660.
4. Gupton, J. T.; Krolikowski, D. A.; Yu, R. H.; Riesinger, S. W.; Sikorski, J. A. J. Org. Chem. 1990, 55, 4735–4740. Gallagher,
P. T.; Palmer, J. L.; Morgan, S. E. J. Chem. Soc., Perkin Trans. 1 1990, 3212–3214.
5. Campi, E. M.; Jackson, W. R.; Nilsson, Y. Tetrahedron Lett. 1991, 32, 1093–1094.
6. Ritter, K. Synthesis 1993, 735–762.
7. Preparation of vinyl triflate (2): To a stirred solution of 1-benzyl-3-pyrrolidinone (1) in anhydrous THF under nitrogen at
−78°C was added sodium bis(trimethylsilyl)amide (1.0 M solution in THF) dropwise. After stirring at −78°C for 1 h, a
solution of N-phenyltrifluoromethanesulfonimide in anhydrous THF was quickly added to the mixture. After agitating at
−78°C for 10 min, the slurry was warmed slowly to 0°C and stirred at 0°C for 3 h. The solvent was removed, and the crude

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residue was taken up in CH2Cl2 and washed with water. Drying and evaporation of the organic extracts gave an oil, which
was purified by flash chromatography. 1H NMR (300 MHz, CDCl3) δ 3.62 (s, 4H), 3.82 (s, 2H), 5.69 (s, 1H), 7.25–7.35
(m, 5H); 13C NMR (75 MHz, CDCl3) δ 56.4, 56.5, 60.2, 113.9, 118.5 (d, J=318.9 Hz), 127.4, 128.52, 128.54, 137.9, 145.1.
8. Zheng, Q.; Yang, Y.; Martin, A. R. Heterocycles 1994, 37, 1761–1772.
9. Preparation of 3-arylpyrroles (3): A mixture of vinyl triflate, boronic acid, Pd(PPh3)4 and KOAc in dioxane was heated
to 100°C overnight. The product was extracted with CH2Cl2, washed with brine and dried over Na2SO4. Isolation by flash
1
chromatography gave following compounds. Representative data for the selected compound (3a): H NMR (300 MHz,
CDCl3) δ 5.08 (s, 2H), 6.46 (m, 1H), 6.73 (m, 1H), 6.94 (m, 1H), 7.00–7.49 (m, 9H); 13C NMR (75 MHz, CDCl3) δ 54.0,
106.9, 115.8 (d, J=21.2 Hz), 118.1, 122.8, 124.7, 126.8 (d, J=7.7 Hz), 127.5, 128.4, 129.2, 132.4 (d, J=3.2 Hz), 138.2,
161.5 (d, J=242.0 Hz); FAB-MS m/z 252.0 ([M+H]+, calcd 252.3).
10. Hudlický, M. Oxidations in Organic Chemistry; American Chemical Society: Washington, DC, 1990; pp. 38, 50–51.
11. There is literature about the oxidation of pyrroline to pyrrole by Pd(PPh3)4: Bäckvall, J.-E.; Nyström, J.-E. J. Chem. Soc.,
Chem. Commun. 1981, 59–61.